US3284503A - 2-cycloalkylmethylamino-benzhydrols and benzophenones - Google Patents

2-cycloalkylmethylamino-benzhydrols and benzophenones Download PDF

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US3284503A
US3284503A US427079A US42707965A US3284503A US 3284503 A US3284503 A US 3284503A US 427079 A US427079 A US 427079A US 42707965 A US42707965 A US 42707965A US 3284503 A US3284503 A US 3284503A
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chlorobenzophenone
cyclopropylmethyl
formula
phthalimidoacetyl
solution
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US427079A
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Freeman H Mcmillan
Pattison Ian
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Warner Lambert Co LLC
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Warner Lambert Pharmaceutical Co
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Priority claimed from US262221A external-priority patent/US3192199A/en
Priority to GB18838/65A priority Critical patent/GB1040163A/en
Priority to GB7285/64A priority patent/GB1040162A/en
Priority to DEW36239A priority patent/DE1229098B/en
Priority to FR965405A priority patent/FR1394287A/en
Priority to BE644425A priority patent/BE644425A/xx
Priority to CH1156567A priority patent/CH476690A/en
Priority to BR157222/64A priority patent/BR6457222D0/en
Priority to DK101064AA priority patent/DK116511B/en
Priority to CH1156467A priority patent/CH471774A/en
Priority to CH249064A priority patent/CH446357A/en
Priority to CH1156267A priority patent/CH459209A/en
Priority to CH1156367A priority patent/CH466272A/en
Priority to SE2503/64A priority patent/SE320376B/xx
Priority to SE15036/65A priority patent/SE326177B/xx
Application filed by Warner Lambert Pharmaceutical Co filed Critical Warner Lambert Pharmaceutical Co
Priority to US427091A priority patent/US3221050A/en
Priority to US427079A priority patent/US3284503A/en
Priority to US427141A priority patent/US3304313A/en
Priority to DK76665AA priority patent/DK129001B/en
Priority to DK76465AA priority patent/DK117069B/en
Priority to DK76565AA priority patent/DK128891B/en
Priority to DK76765AA priority patent/DK129003B/en
Priority to SE15038/65A priority patent/SE326179B/xx
Priority to SE15037/65A priority patent/SE326178B/xx
Publication of US3284503A publication Critical patent/US3284503A/en
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D243/00—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms
    • C07D243/06—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4
    • C07D243/10—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4 condensed with carbocyclic rings or ring systems
    • C07D243/14—1,4-Benzodiazepines; Hydrogenated 1,4-benzodiazepines
    • C07D243/16—1,4-Benzodiazepines; Hydrogenated 1,4-benzodiazepines substituted in position 5 by aryl radicals
    • C07D243/18—1,4-Benzodiazepines; Hydrogenated 1,4-benzodiazepines substituted in position 5 by aryl radicals substituted in position 2 by nitrogen, oxygen or sulfur atoms
    • C07D243/24—Oxygen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C233/00—Carboxylic acid amides
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
    • C07D209/44—Iso-indoles; Hydrogenated iso-indoles
    • C07D209/48—Iso-indoles; Hydrogenated iso-indoles with oxygen atoms in positions 1 and 3, e.g. phthalimide
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D243/00—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms
    • C07D243/06—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4
    • C07D243/10—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4 condensed with carbocyclic rings or ring systems
    • C07D243/14—1,4-Benzodiazepines; Hydrogenated 1,4-benzodiazepines
    • C07D243/16—1,4-Benzodiazepines; Hydrogenated 1,4-benzodiazepines substituted in position 5 by aryl radicals
    • C07D243/18—1,4-Benzodiazepines; Hydrogenated 1,4-benzodiazepines substituted in position 5 by aryl radicals substituted in position 2 by nitrogen, oxygen or sulfur atoms
    • C07D243/24—Oxygen atoms
    • C07D243/30—Preparation including building-up the benzodiazepine skeleton from compounds already containing hetero rings
    • C07D243/32—Preparation including building-up the benzodiazepine skeleton from compounds already containing hetero rings containing a phthalimide or hydrogenated phthalimide ring system

Definitions

  • This invention relates to a new and novel process for the production of substituted 1,4-benzodiazepines of the formula:
  • R represents a cycloalkylmethyl group such as cyclopropylmethyl, cyclobutylmethyl or cyclopentylmethyl and R represents hydrogen, lower alkyl, lower alkoxy or halogen such as chlorine or bromine.
  • This invention also relates to certain novel intermediates obtained during the process.
  • the compounds of the above formula are useful as tranquilizers. For example, they exhibit anti-anxiety and sedative activity without undesirable side-effects such as hypnosis. In addition, they are useful as intermediates for the production of other substituted benzodiazepines.
  • these substituted 1,4-benzodiazepines are prepared by the following sequence of steps.
  • Step I of our novel process comprises treating a 2- amino-halobenzophenone such as Z-amino-S-chlorobenzophenone:
  • the above reaction product can be readily separated from the mother liquor by the removal of the solvents.
  • Step II comprises reducing the compound obtained in accordance with Step I with an excess of a reducing agent such as lithium aluminum hydride followed by aqueous hydrolysis to form the corresponding 2-cycloalkylmethylaminohalobenzhydrol such as, for example, 2-cyclopropylmethylamino-S-chlorobenzhydrol having the following structural formula:
  • Step III comprises oxidizing the benzhy-drol group of the product of Step II with an excess of manganese dioxide to yield, for example, 2-cyclopropylmethylamino-5- chlorobenzophenone of the formula:
  • Step IV comprises the preparation of a phthalimidoacetyl derivative of the product obtained in accordance with Step III.
  • a phthalimidoacetyl derivative of the product obtained in accordance with Step III 2-(N-phthalimidoacetyl-N- cyclopropylmethyl)-amino-5-chlorobenzophenone of the formula:
  • Step III may be prepared by refluxing one mole of 2-cyclopr-opylmethylamino-5-chlorobenzophenone (obtained in Step III) in tetrahydrofuran with two moles of phthalimidoacetyl chloride.
  • the reaction product is readily obtained by removal of the solvent.
  • Step V the fin al step, comprises the ring closure with hydrazine hydrate of the phthalimidoacetyl derivatives obtained in accordance with Step IV thus forming the novel compounds of this invention.
  • a solution of 2-(N-phthalimidoacetyl-N-cyclopropylmethyl)-amino-5-chlorobenzophenone in a mixture of chloroform and ethanol is reacted with an excess of hydrazine hydrate to give a compound of the formula:
  • the reaction is refluxed 2 /2 hours and allowed to cool to room temperature.
  • the solvent is then removed under vacuum to obtain 2-cycl-opropylcarbonylamid0-5-chl0robenzophenone as a residue which is dissolved in 1 liter of methylene chloride, washed twice with 5% hydrochloric acid, and then twice with potassium hydroxide.
  • the methylene chloride solution is then dried over anhydrous magnesium sulfate, filtered and the solvent removed under vacuum.
  • the residue is recrystallized from 1500 ml. of methanol, charcoaling the hot solution to give 356 g. of 2-cyclopr0pylcarbonylamido-S-chlorobenzophenone, M.P. 105 105.5 C. (69% yield), containing in the infrared a single unresolved carbonyl band at 1670 cm.-
  • Example 2 -2-cyel0propylmethylamin0-5-chl0r0benzhydrol
  • a solution of 94.8 g. (2.47 moles) of lithium aluminum hydride in 1.2 liters of tetrahydrofuran is added with stirring a solution of 356 g. (1.18 moles) of 2-cyclopropyl-carbonyl-amido-S-chlorobenzophenone in 1.8 liters of tetrahydrofuran.
  • the addition takes place 80 minutes while maintaining gentle refluxing, and the reaction mixture is then refluxed overnight and allowed to cool to room temperature over a period of 3 days.
  • the complex formed in the reaction mixture is then hydrolyzed with water.
  • Example 4 Preparati0n of 2(N-phthalimidoacetyl-N- cyclopropylmethyl) -amin0-5-ehlorobenzophenone
  • To a solution of 36.0 g. (0.126 mole) of 2-cyclopropylmethylamino-S-chlor-obenzophenone in 500 ml. of tetrahydrofuran is added 50.7 g. (0.252 mole) of phthalimidoacetyl chloride.
  • the resulting solution is refluxed for 16 to 24 hours, the solvent removed under vacuum, the residual oil crystallized from 200 ml. of ethanol and recrystallized from 500 ml.
  • Example 5 Preparation of 1 -cyclopr0py [methyl-5- phenyl-7-chl0r0-1H-1,4-benz0diazepine-2 (3H) one To a solution of 39.5 g. (0.0845 mole) of 2(N-phthalimidoacetyl-N-cyclopropylmethyl)amino-5 chlorobenzophenone in a mixture of 423 ml. of chloroform and 423 ml. of ethanol is added 9.52 g. (0.1903 mole) of hydrazine hydrate and 9.52 ml. of water. This solution is allowed to stand at room temperature. In three hours a precipitate begins to form in the solution.
  • R is a member selected from the group consisting of cyclopropylmethyl, cyclobutylmethyl and cyclopentylmet'hyl and R is a member of the group consisting of hydrogen, chlorine, bromine, lower alkyl and lower alkoxy.
  • R is a member selected from the group conpages 5 75 954 sisting of cyclopropylmethyl, cyclobutylmethyl and cyclopentylmethyl and R is a membercf the group consist- 15 CHARLES B, PARKER, Primary Examiner, iggvelefanlgirlogen, chlorine, bromine, lower alkyl and JOHN D. RANDOLPH Examiner.

Description

United States Patent Ofifice Patented Nov. 8, 1966 This application is a divisional application of Serial No. 262,221, filed March 1, 1963, now US. Pat. No. 3,192,199.
This invention relates to a new and novel process for the production of substituted 1,4-benzodiazepines of the formula:
wherein R represents a cycloalkylmethyl group such as cyclopropylmethyl, cyclobutylmethyl or cyclopentylmethyl and R represents hydrogen, lower alkyl, lower alkoxy or halogen such as chlorine or bromine.
This invention also relates to certain novel intermediates obtained during the process.
The compounds of the above formula are useful as tranquilizers. For example, they exhibit anti-anxiety and sedative activity without undesirable side-effects such as hypnosis. In addition, they are useful as intermediates for the production of other substituted benzodiazepines.
In accordance with our invention, these substituted 1,4-benzodiazepines are prepared by the following sequence of steps.
Step I of our novel process comprises treating a 2- amino-halobenzophenone such as Z-amino-S-chlorobenzophenone:
dissolved in a mixture of tetrahydrofuran and triethylamine with an equal molar ratio of the desired cycloalkanecarboxylic acid chloride such as, for example, cyclopropanecarboxylic acid chloride, followed by refluxing the resulting reaction mixture to yield a 2-cyclopropylcarbonylamido-S-chlorobenzophenone of the formula:
The above reaction product can be readily separated from the mother liquor by the removal of the solvents.
Step II comprises reducing the compound obtained in accordance with Step I with an excess of a reducing agent such as lithium aluminum hydride followed by aqueous hydrolysis to form the corresponding 2-cycloalkylmethylaminohalobenzhydrol such as, for example, 2-cyclopropylmethylamino-S-chlorobenzhydrol having the following structural formula:
Cl OHOH Step III comprises oxidizing the benzhy-drol group of the product of Step II with an excess of manganese dioxide to yield, for example, 2-cyclopropylmethylamino-5- chlorobenzophenone of the formula:
Step IV comprises the preparation of a phthalimidoacetyl derivative of the product obtained in accordance with Step III. For example, 2-(N-phthalimidoacetyl-N- cyclopropylmethyl)-amino-5-chlorobenzophenone of the formula:
may be prepared by refluxing one mole of 2-cyclopr-opylmethylamino-5-chlorobenzophenone (obtained in Step III) in tetrahydrofuran with two moles of phthalimidoacetyl chloride. The reaction product is readily obtained by removal of the solvent.
Step V, the fin al step, comprises the ring closure with hydrazine hydrate of the phthalimidoacetyl derivatives obtained in accordance with Step IV thus forming the novel compounds of this invention. Thus, for example, when a solution of 2-(N-phthalimidoacetyl-N-cyclopropylmethyl)-amino-5-chlorobenzophenone in a mixture of chloroform and ethanol is reacted with an excess of hydrazine hydrate to give a compound of the formula:
CH -A; I o C Example I.2-eyelopr0pylcarbonylamid0-5-chl0r0- benzophenone To 400.5 g. (1.73 moles) of 2-amino-5-chlorobenzophenone dissolved in 220 g. (2.18 moles) of triethylamine and 3.5 liters of tetrahydrofuran is added cautiously 181 'g. (1.73 moles) of cyclopropanecarboxylic acid chloride.
The reaction is refluxed 2 /2 hours and allowed to cool to room temperature. The solvent is then removed under vacuum to obtain 2-cycl-opropylcarbonylamid0-5-chl0robenzophenone as a residue which is dissolved in 1 liter of methylene chloride, washed twice with 5% hydrochloric acid, and then twice with potassium hydroxide. The methylene chloride solution is then dried over anhydrous magnesium sulfate, filtered and the solvent removed under vacuum. The residue is recrystallized from 1500 ml. of methanol, charcoaling the hot solution to give 356 g. of 2-cyclopr0pylcarbonylamido-S-chlorobenzophenone, M.P. 105 105.5 C. (69% yield), containing in the infrared a single unresolved carbonyl band at 1670 cm.-
Example 2.-2-cyel0propylmethylamin0-5-chl0r0benzhydrol To a slurry of 94.8 g. (2.47 moles) of lithium aluminum hydride in 1.2 liters of tetrahydrofuran is added with stirring a solution of 356 g. (1.18 moles) of 2-cyclopropyl-carbonyl-amido-S-chlorobenzophenone in 1.8 liters of tetrahydrofuran. The addition takes place 80 minutes while maintaining gentle refluxing, and the reaction mixture is then refluxed overnight and allowed to cool to room temperature over a period of 3 days. The complex formed in the reaction mixture is then hydrolyzed with water. During the hydrolysis, 500 milliliters of tetrahydrofuran is added to facilitate stirring. At a point where the flocc-ulant white precipitate settles quickly when stirring is interrupted, the mixture is filtered, the filter cake washed with solvent, the combined filtrates dried over magnesium sulfate, filtered and the solvent removed under vacuum to obtain 2-cyclopropylmethylarnino-5-chlorobenzhydrol as a residue. The residue is recrystallized tfrom 1300 ml. of Skelly B, giving 315 g. of 2-cyclopropylmethylamino-S-chlorobenzhydrol, M.P. 85-855 C. (93% yield).
methylamino-S-chlorobenzhydrol in 4 liters of benzene is added 453.6 g. (5.22 moles) of manganese dioxide, freshly prepared according to the method of Attenburrow et al., J.C.S. 1952, 1104. The mixture is then refluxed for 1% hours, filtered, and the filtrate evaporated under vacuum. The reddish residue is recrystallized from 510 ml. of acetone-10% water, giving 181 g. of pure 2-cyclopropylmethylamine-5-chlorobenzophenone, M.P. 79-80 C. (58% yield.) Upon concentration of the mother liquor a second crop of 2-cyclopropylmethylamino-5- chlorobenzophenone weighing 34.1 g. and melting at 76.5 7 8 C. are obtained.
Analysis.Calcd: C, 71.45; H, 5.64; Cl, 12.41. Found: C, 71.67; H, 5.82; Cl, 12.68; 12.71.
Example 4.Preparati0n of 2(N-phthalimidoacetyl-N- cyclopropylmethyl) -amin0-5-ehlorobenzophenone To a solution of 36.0 g. (0.126 mole) of 2-cyclopropylmethylamino-S-chlor-obenzophenone in 500 ml. of tetrahydrofuran is added 50.7 g. (0.252 mole) of phthalimidoacetyl chloride. The resulting solution is refluxed for 16 to 24 hours, the solvent removed under vacuum, the residual oil crystallized from 200 ml. of ethanol and recrystallized from 500 ml. of 80% ethanol-20% tetrahydrofuran giving 44.7 g. of 2(N-phthalimidoacetyl-N- cyclopropylmethyl)-amino-5 chlorobenzophenone, M.P. 163164 C. (75% yield.)
Analysis.-Calcd: C, 68.57; H, 4.48; N, 5.92. Found: C, 68.36; H, 4.29; N, 5.85.
Example 5 .Preparation of 1 -cyclopr0py [methyl-5- phenyl-7-chl0r0-1H-1,4-benz0diazepine-2 (3H) one To a solution of 39.5 g. (0.0845 mole) of 2(N-phthalimidoacetyl-N-cyclopropylmethyl)amino-5 chlorobenzophenone in a mixture of 423 ml. of chloroform and 423 ml. of ethanol is added 9.52 g. (0.1903 mole) of hydrazine hydrate and 9.52 ml. of water. This solution is allowed to stand at room temperature. In three hours a precipitate begins to form in the solution. After standing 16 to 24 hours a voluminous pulpy white precipitate forms. The solvents are removed under vacuum while keeping the temperature under 40 C. and the residue is partitioned between dilute ammonia water and ether. The aqueous layer is separated and washed with ether, the ether extracted with 5% hydrochloric acid, the acidic solution is made basic with 10% sodium hydroxide and again extracted with ether. Since some spontaneous crystallization occurs in the ether, the solvent is removed without drying under vacuum and the residue is recrystallized from 35 ml. of ethanol giving 18.0 of l-cyclopropylmethyl-S-phenyl-7-chloro-1H-1,4-benzodiazepine 2(3H) one, M.P. 146 C. (65% yield.)
Analysis.Calc"d: C, 70.25; H, 5.28; H, 8.62. Found: C, 70.35; H, 5.41; H, 8.42.
It is understood that the foregoing detailed description is given merely by way of illustration and that many variations may be made therein without departing from the spirit of our invention.
Having described our invention, what we desire to secure by Letters Patent is:
We claim:
1. A compound of the formula:
in which R is a member selected from the group consisting of cyclopropylmethyl, cyclobutylmethyl and cyclopentylmet'hyl and R is a member of the group consisting of hydrogen, chlorine, bromine, lower alkyl and lower alkoxy.
5 6 2. Z-cyclopropylmethylamino-5-ch1orobenzophenone. References Cited by the Examiner 3. A compound of the formula: UNITED STATES PATENTS R, 2,993,062 7/1961 Moyle et a1. 260562 g 5 3,152,179 10/1964 Garland 260--570.5 X B2 3,153,093 10/1964 Horrom et a1 260570.5
CHOH OTHER REFERENCES Fischer et a1.: German Auslegeschrift 1,005,784 (K1 451 5), 2 pages spec.
Larsson, Chemical Abstracts, vol. 45, page 1494 (1951).
Turner, Jour. American Chemical Society, vol. 76, in which R is a member selected from the group conpages 5 75 954 sisting of cyclopropylmethyl, cyclobutylmethyl and cyclopentylmethyl and R is a membercf the group consist- 15 CHARLES B, PARKER, Primary Examiner, iggvelefanlgirlogen, chlorine, bromine, lower alkyl and JOHN D. RANDOLPH Examiner.
4. 2-cyc1opropylmethylamino-5-chlorobenzhydrol. N. TROUSOF, R. V. HINES, Assistant Examiner.

Claims (1)

1. A COMPOUND OF THE FORMULA: 1-(R1-NH-),2-(PHENYL-CO-),R2-BENZENE IN WHICH R1 IS A MEMBER SELECTED FROM THE GROUP CONSISTING OF CYCLOPROPYLMETHYL, CYCLOBUTYLMETHYL AND CYCLOPENTYLMETHYL AND R2 IS A MEMBER OF THE GROUP CONSISTING OF HYDROGEN, CHLORINE, BROMINE, LOWER ALKYL AND LOWER ALKOXY.
US427079A 1963-03-01 1965-01-21 2-cycloalkylmethylamino-benzhydrols and benzophenones Expired - Lifetime US3284503A (en)

Priority Applications (23)

Application Number Priority Date Filing Date Title
GB18838/65A GB1040163A (en) 1963-03-01 1964-02-21 Derivatives of benzophenone and benzhydrol
GB7285/64A GB1040162A (en) 1963-03-01 1964-02-21 Process for the production of 1-cycloalkylmethyl-substituted 1,4-benzodiazepines
DEW36239A DE1229098B (en) 1963-03-01 1964-02-24 Process for the preparation of substituted 5-phenyl-1, 2-dihydro-3 H-1, 4-benzodiazepinone (2) derivatives
BE644425A BE644425A (en) 1963-03-01 1964-02-27
FR965405A FR1394287A (en) 1963-03-01 1964-02-27 Process for the preparation of 1, 4-substituted benzodiazepines
BR157222/64A BR6457222D0 (en) 1963-03-01 1964-02-28 PROCESS FOR THE PRODUCTION OF REPLACED BENZODIAZEPIN COMPOUNDS
DK101064AA DK116511B (en) 1963-03-01 1964-02-28 Process for the preparation of substituted 1,4-benzodiazepine compounds.
CH1156467A CH471774A (en) 1963-03-01 1964-02-28 Process for the preparation of cycloalkylmethylamino-benzhydrols
CH249064A CH446357A (en) 1963-03-01 1964-02-28 Process for the preparation of substituted 1,4 benzodiazepine compounds
CH1156267A CH459209A (en) 1963-03-01 1964-02-28 Process for the preparation of phthalimidoacetyl compounds
CH1156367A CH466272A (en) 1963-03-01 1964-02-28 Process for the preparation of cycloalkylmethylaminobenzophenones
CH1156567A CH476690A (en) 1963-03-01 1964-02-28 Process for the preparation of 2-cycloalkylcarbonylamino compounds
SE2503/64A SE320376B (en) 1963-03-01 1964-02-29
SE15036/65A SE326177B (en) 1963-03-01 1964-02-29
US427091A US3221050A (en) 1963-03-01 1965-01-21 2-cycloalkylcarbonylamido-5-halobenzophenones
US427079A US3284503A (en) 1963-03-01 1965-01-21 2-cycloalkylmethylamino-benzhydrols and benzophenones
US427141A US3304313A (en) 1963-03-01 1965-01-21 2-(nu-phthalimidoacetyl-nu-cycloalkylmethyl)-aminobenzophenone derivatives
DK76465AA DK117069B (en) 1963-03-01 1965-02-12 Phthalimidoacetyl compounds for use as intermediates in the preparation of 5-phenyl-1H-1,4-benzodiazepin-2 (3H) -ones.
DK76665AA DK129001B (en) 1963-03-01 1965-02-12 Cycloalkylmethylaminobenzhydrol compounds for use as intermediates in the preparation of 1-cycloalkylmethyl-5-phenyl-1H-1,4-benzodiazepin-2 (3H) -ones.
DK76565AA DK128891B (en) 1963-03-01 1965-02-12 Cycloalkylmethylaminobenzophenone derivatives for use as intermediates in the preparation of 1-cycloalkylmethyl-5-pheny-1H-1,4-benzodiazepin-2 (3H) -ones.
DK76765AA DK129003B (en) 1963-03-01 1965-02-12 2-Cycloalkylcarbonylamido compounds for use as intermediates in the preparation of 1-cycloalkylmethyl-5-phenyl-1H-1,4-benzodiazepin-2 (3H) -ones.
SE15038/65A SE326179B (en) 1963-03-01 1965-11-22
SE15037/65A SE326178B (en) 1963-03-01 1965-11-22

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US262221A US3192199A (en) 1963-03-01 1963-03-01 Process for the production of 1-cycloalkyl derivatives of 1, 4-benzodiazepine
US427079A US3284503A (en) 1963-03-01 1965-01-21 2-cycloalkylmethylamino-benzhydrols and benzophenones
US427141A US3304313A (en) 1963-03-01 1965-01-21 2-(nu-phthalimidoacetyl-nu-cycloalkylmethyl)-aminobenzophenone derivatives

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US427141A Expired - Lifetime US3304313A (en) 1963-03-01 1965-01-21 2-(nu-phthalimidoacetyl-nu-cycloalkylmethyl)-aminobenzophenone derivatives
US427079A Expired - Lifetime US3284503A (en) 1963-03-01 1965-01-21 2-cycloalkylmethylamino-benzhydrols and benzophenones

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BE (1) BE644425A (en)
BR (1) BR6457222D0 (en)
CH (3) CH466272A (en)
DE (1) DE1229098B (en)
DK (5) DK116511B (en)
FR (1) FR1394287A (en)
GB (2) GB1040162A (en)
SE (4) SE320376B (en)

Cited By (2)

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US3691157A (en) * 1970-08-12 1972-09-12 Rodney Ian Fryer Preparation of 7-substituted-1-(2-diethylaminoethyl)-5-(2-halophenyl)-1,3-dihydro-2h-1,4-benzodiazepin-2-ones
US3925364A (en) * 1967-09-22 1975-12-09 Sumitomo Chemical Co Benzodiazepine derivatives

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US3549623A (en) * 1968-11-14 1970-12-22 Warner Lambert Pharmaceutical 7-r1-1-(r2)-3-hydroxy-5-phenyl-1h-1,4-benzodiazepin-2(3h)-one
USRE31071E (en) * 1971-12-09 1982-11-02 Deutsche Gold- Und Silber-Scheideanstalt Vormals Roessler 6-Aza-3H-1,4-benzodiazepines
US4008223A (en) * 1971-12-09 1977-02-15 Deutsche Gold- Und Silber-Scheideanstalt Vormals Roessler 6-Aza-3H-1,4-benzodiazepines
KR900003529B1 (en) * 1985-07-29 1990-05-21 오르토 파마슈티컬 코포레이션 Process for preparing 2-acyl-3,4-di'alkoxyanilines

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US3153093A (en) * 1961-11-22 1964-10-13 Abbott Lab Amino derivatives of nu-cyclopropylbenzylamines

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US2993062A (en) * 1959-10-22 1961-07-18 Dow Chemical Co Carboxamides of nu-pentachlorophenylethylenediamine
US3153093A (en) * 1961-11-22 1964-10-13 Abbott Lab Amino derivatives of nu-cyclopropylbenzylamines
US3152179A (en) * 1963-03-22 1964-10-06 Searle & Co 2-(hydroxy/oxy)-nu, nu-di (lower alkyl)-5-(6-methoxy-2-naphthyl) cyclopentane-acetamides and congeners

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3925364A (en) * 1967-09-22 1975-12-09 Sumitomo Chemical Co Benzodiazepine derivatives
US3691157A (en) * 1970-08-12 1972-09-12 Rodney Ian Fryer Preparation of 7-substituted-1-(2-diethylaminoethyl)-5-(2-halophenyl)-1,3-dihydro-2h-1,4-benzodiazepin-2-ones

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DK128891B (en) 1974-07-22
DK129001B (en) 1974-08-05
DK117069B (en) 1970-03-16
DE1229098B (en) 1966-11-24
US3304313A (en) 1967-02-14
GB1040163A (en) 1966-08-24
DK129003B (en) 1974-08-05
SE320376B (en) 1970-02-09
DK116511B (en) 1970-01-19
BR6457222D0 (en) 1973-07-17
SE326179B (en) 1970-07-20
BE644425A (en) 1964-06-27
CH446357A (en) 1967-11-15
SE326177B (en) 1970-07-20
GB1040162A (en) 1966-08-24
CH459209A (en) 1968-07-15
FR1394287A (en) 1965-04-02
SE326178B (en) 1970-07-20
CH466272A (en) 1968-12-15

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